Refractory Intracranial Hypertension Research Articles

Autonomic Nervous System Activity during Refractory Rise in Intracranial Pressure.

Refractory intracranial hypertension (RIH) is a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment. Recent reports suggest that the autonomic nervous system (ANS) activity may be altered during changes in ICP. Our study aimed to assess ANS activity during RIH and the causal relationship between rising in ICP and autonomic activity. We reviewed retrospectively 24 multicenter (Cambridge, Tromso, Berlin) patients in whom RIH developed as a pre-terminal event after acute brain injury (ABI). They were monitored with ICP, arterial blood pressure (ABP), and electrocardiography (ECG) using ICM+ software. Parameters reflecting autonomic activity were computed in time and frequency domain through the measurement of heart rate variability (HRV) and baroreflex sensitivity (BRS). Our results demonstrated that a rise in ICP was associated to a significant rise in HRV and BRS with a higher significance level in the high-frequency HRV (p < 0.001). This increase was followed by a significant decrease in HRV and BRS above the upper-breakpoint of ICP where ICP pulse-amplitude starts to decrease whereas the mean ICP continues to rise. Temporality measured with a Granger test suggests a causal relationship from ICP to ANS. The above results suggest that a rise in ICP interacts with ANS activity, mainly interfacing with the parasympathetic-system. The ANS seems to react to the rise in ICP with a response possibly focused on maintaining the cerebrovascular homeostasis. This happens until the critical threshold of ICP is reached above which the ANS variables collapse, probably because of low perfusion of the brain and the central autonomic network.

Methodological Consideration on Monitoring Refractory Intracranial Hypertension and Autonomic Nervous System Activity.

Refractory intracranial hypertension (RIH) refers to a dramatic increase in intracranial pressure (ICP) that cannot be controlled by treatment and leads to patient death. Detrimental sequelae of raised ICP in acute brain injury (ABI) are unclear because the underlying physiopathological mechanisms of raised ICP have not been sufficiently investigated. Recent reports have shown that autonomic activity is altered during changes in ICP. The aim of our study was to evaluate the feasibility of assessing autonomic activity during RIH with our adopted methodology. We selected 24 ABI patients for retrospective review who developed RIH. They were monitored based on ICP, arterial blood pressure, and electrocardiogram using ICM+ software. Secondary parameters reflecting autonomic activity were computed in time and frequency domains through the continuous measurement of heart rate variability and baroreflex sensitivity. The results of the analysis will be presented later in a full paper. This preliminary analysis shows the feasibility of the adopted methodology.

Comparison of Lumboperitoneal Shunt and Stereotactic Ventriculoperitoneal Shunt in the Treatment of Refractory Idiopathic Intracranial Hypertension: A Case Report and Literature Review

Idiopathic Intracranial Hypertension (IIH) or Pseudotumor Cerebri (PTC) is a disorder of young obese females and characterized by headache, papilledema and raised intracranial pressure. However, it is in the absence of known pathological cause. Due to the uncertainty of etiology, it may lead to misdiagnosis and grave clinical prognosis. IIH is typically treated with Lumboperitoneal Shunting (LPS) and Ventriculoperitoneal Shunting (VPS), but shunts are prone to dysfunctions and infection, resulting in recurrent headaches in many patients after this treatment. We report a case of 41-year-old obese female (BMI: 30.9) with IIH, who has a history of hypertension (Blood pressure: 150/100 mmHg) and elevated intracranial pressure (Open pressure: 450 mmH2 O). After the failure of several medical treatments, the patient was offered LPS because of vision loss and headache, but the postoperative symptoms (intermittent headache, mainly total craniocerebral prickling pain with neck and shoulder pain) were not significantly relieved for 11 years. Therefore, considering the blockage of the primary shunt tube and the small ventricle in the patient, it has difficulty in puncture ventricle puncture. We have to treat with the stereotactic VPS (SVPS) for her exacerbation symptoms. More surprisingly, the hypertension was in the normal range (&lt;115/80 mmHg) after the surgery (without taking antihypertensive medication). To compare the surgical therapeutic effects and complications of LPS and the SVPS in the treatment of idiopathic intracranial hypertension. Cerebrospinal Fluid (CSF) diversion with VPS or LPS is usually performed when the main symptom is vision loss; it also stabilizes headache and papilledema. LPS significantly alleviates symptoms in the short term, but due to excessive shunt of LPS for a long time, it is easy to be complicated with Chiari malformation and slit ventricle syndrome. Therefore, we encourage operating the SVPS on our patients for the favorable long-term outcome.

Temporal effects of barbiturate coma on intracranial pressure and compensatory reserve in children with traumatic brain injury

BackgroundThe aim was to study the effects of barbiturate coma treatment (BCT) on intracranial pressure (ICP) and intracranial compensatory reserve (RAP index) in children (< 17 years of age) with traumatic brain injury (TBI) and refractory intracranial hypertension (RICH).MethodsHigh-resolution monitoring data were used to study the effects of BCT on ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and RAP index. Four half hour long periods were studied: before bolus injection and at 5, 10, and 24 hours thereafter, respectively, and a fifth tapering period with S-thiopental between < 100 and < 30 μmol/L. S-thiopental concentrations and administered doses were registered.ResultsSeventeen children treated with BCT 2007–2017 with high-resolution data were included; median age 15 (range 6–17) and median Glasgow coma score 7 (range 3–8). Median time from trauma to start of BCT was 44.5 h (range 2.5–197.5) and from start to stop 99.0 h (range 21.0–329.0). Median ICP was 22 (IQR 20–25) in the half hour period before onset of BCT and 16 (IQR 11–20) in the half hour period 5 h later (p = 0.011). The corresponding figures for CPP were 65 (IQR 62–71) and 63 (57–71) (p > 0.05). The RAP index was in the half hour period before onset of BCT 0.6 (IQR 0.1–0.7), in the half hour period 5 h later 0.3 (IQR 0.1–0.7) (p = 0.331), and in the whole BCT period 0.3 (IQR 0.2–0.4) (p = 0.004). Eighty-two percent (14/17) had favorable outcome (good recovery = 8 patients and moderate disability = 6 patients).ConclusionBCT significantly reduced ICP and RAP index with preserved CPP. BCT should be considered in case of RICH.

Does electroencephalographic burst suppression still play a role in the perioperative setting?

With the widespread use of electroencephalogram [EEG] monitoring during surgery or in the Intensive Care Unit [ICU], clinicians can sometimes face the pattern of burst suppression [BS]. The BS pattern corresponds to the continuous quasi-periodic alternation between high-voltage slow waves [the bursts] and periods of low voltage or even isoelectricity of the EEG signal [the suppression] and is extremely rare outside ICU and the operative room. BS can be secondary to increased anesthetic depth or a marker of cerebral damage, as a therapeutic endpoint [i.e., refractory status epilepticus or refractory intracranial hypertension]. In this review, we report the neurophysiological features of BS to better define its role during intraoperative and critical care settings.

Novel Decompressive Hemicraniectomy Technique for Traumatic Brain Injury: Technical Note

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality across all age groups. Decompressive hemicraniectomy is the treatment for TBI-related refractory intracranial hypertension. The traditional technique for this procedure can result in wound complications due to injury of the scalp flap's vascular supply, namely the superficial temporal and postauricular arteries. In this technical note we describe our experience using a novel technique that preserves both vascular territories by placing the inferior aspect of the incision posterior to the ear as opposed to anterior to it. This modification has the potential to reduce wound healing complications, especially in those at higher risk, while also reducing operative time by avoiding temporalis muscle incision and closure during procedure. After performing hospital chart review, a total of 7 patients were found who underwent this hemicraniectomy technique for severe TBI. Of these, 5 patients had this performed on the left side, and 2 patients had this performed on the right side. Six of the patients had an accompanying subdural hematoma, whereas 1 patient had no intracranial hemorrhage present. In each case, both the superficial temporal and postauricular arteries were preserved, and rapid healing of the scalp flap occurred. In addition to providing a large bone window to allow the brain to swell, this technique has the potential to reduce complications of wound healing by preserving the vascular supply of the scalp flap and reduce operative times by minimizing temporalis muscle dissection.

Pentobarbital Coma With Therapeutic Hypothermia for Treatment of Refractory Intracranial Hypertension in Traumatic Brain Injury Patients: A Single Institution Experience.

IntroductionTraumatic brain injury (TBI) results in primary and secondary brain injuries. Secondary brain injury can lead to cerebral edema resulting in increased intracranial pressure (ICP) secondary to the rigid encasement of the skull. Increased ICP leads to decreased cerebral perfusion pressure which leads to cerebral ischemia. Refractory intracranial hypertension (RICH) occurs when ICP remains elevated despite first-tier therapies such as head elevation, straightening of the neck, analgesia, sedation, paralytics, cerebrospinal fluid (CSF) drainage, mannitol and/or hypertonic saline administration. If unresponsive to these measures, second-tier therapies such as hypothermia, barbiturate infusion, and/or surgery are employed.MethodsThis was a retrospective review of patients admitted at Arrowhead Regional Medical Center from 2008 to 2019 for severe TBI who developed RICH requiring placement into a pentobarbital-induced coma with therapeutic hypothermia. Primary endpoints included mortality, good recovery which was designated at Glasgow outcome scale (GOS) of 4 or 5, and improvement in ICP (goal is <20 mmHg). Secondary endpoints included complications, length of intensive care unit (ICU) stay, length of hospital stay, length of pentobarbital coma, length of hypothermia, need for vasopressors, and decompressive surgery versus no decompressive surgery.ResultsOur study included 18 patients placed in pentobarbital coma with hypothermia for RICH. The overall mortality rate in our study was 50%; with 60% mortality in pentobarbital/hypothermia only group, and 46% mortality in surgery plus pentobarbital/hypothermia group. Maximum ICP prior to pentobarbital/hypothermia was significantly lower in patients who had a prior decompressive craniectomy than in patients who were placed into pentobarbital/hypothermia protocol first (28.3 vs 35.4, p<0.0238). ICP was significantly reduced at 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after pentobarbital and hypothermia treatment. Initial ICP and maximum ICP prior to pentobarbital/hypothermia was significantly correlated with mortality (p=0.022 and p=0.026). Patients with an ICP>25 mmHg prior to pentobarbital/hypothermia initiation had an increased risk of mortality (p=0.0455). There was no statistically significant difference in mean ICP after 24 hours after pentobarbital/hypothermia protocol in survivors vs non-survivors. Increased time to reach 33°C was associated with increased mortality (r=0.47, p=0.047); with a 10.5-fold increase in mortality for >7 hours (OR 10.5, p=0.039).ConclusionProlonged cooling time >7 hours was associated with a 10.5-fold increase in mortality and ICP>25 mmHg prior to initiation of pentobarbital and hypothermia is suggestive of a poor response to treatment. We recommend patients with severe TBI who develop RICH should first undergo a 12 x 15 cm decompressive hemicraniectomy because they have better survival and are more likely to have ICP <25 mmHg as the highest elevation of ICP if the ICP were to become and stay elevated again. Pentobarbital and hypothermia should be initiated if the ICP becomes elevated and sustained above 20 mmHg with a prior decompressive hemicraniectomy and refractory to other medical therapies. However, our data suggests that patients are unlikely to survive if there ICP does not decrease to less than 15mmHg at 8 and 12 hours after pentobarbital/hypothermia and remain less than 20 mmHg within first 48 hours.

Protocol-Based Early Decompressive Craniectomy in a Resource-Constrained Environment: A Tertiary Care Hospital Experience.

Objectives:Decompressive craniectomy (DC) is an emergency life-saving procedure used to treat refractory intracranial hypertension (RICH). The authors aim to analyze their experience with protocol-based early DC (<24 h) in RICH cases diagnosed based on clinical and radiological evidence, without preoperative intracranial pressure monitoring done over 10 years.Materials and Methods:This is a retrospective, observational study which includes 58 consecutive patients who underwent protocol-based early DC by the senior author at a single institution between 2007 and 2017. Background variables and outcome in the form of Glasgow Outcome Score-Extended (GOS-E) at 6 months and 1 year were analyzed.Results:Fourteen patients had traumatic brain injury (TBI), 17 had intracranial hemorrhage (ICH), 14 had malignant cerebral infarcts (MCI), and the reminder 13 patients had other causes. At 6 months, the mortality rate was 22.4%. Good recovery, moderate disability, and severe disability were seen in 13.8%, 17.2%, and 43.1% of patients, respectively. Two patients were in vegetative state. The cutoff for favorable/unfavorable outcome was defined as GOS-E 4–8/1–3. By this application, 63.8% of patients had favorable outcome at 6 months. The favorable outcome in patients of TBI, ICH, and MCI was 57.1%, 58.8%, and 85.7%, respectively.Conclusions:DC helps in obtaining a favorable outcome in selected patients with a defined pathology. The diagnosis of RICH based on clinical and radiological parameters, and protocol-based early DC, is reasonably justified as the way forward for resource-constrained environments. The risk of vegetative state is small.

Management of Australian Patients with Severe Traumatic Brain Injury: Are Potentially Harmful Treatments Still Used?

Clinical trials have shown that intravenous albumin and decompressive craniectomy to treat early refractory intracranial hypertension can cause harm in patients with severe traumatic brain injury (TBI). The extent to which these treatments remain in use is unknown. We conducted a multi-center retrospective cohort study of adult patients with severe TBI admitted to five neurotrauma centers across Australia between April 2013 and March 2015. Patients were identified from local trauma and intensive care unit (ICU) registries and followed until hospital discharge. Main outcome measures were the administration of intravenous albumin, and decompressive craniectomy for intracranial hypertension. Analyses were predominantly descriptive. There were 303 patients with severe TBI, of whom a minority received albumin (6.9%) or underwent early decompressive craniectomy for treatment of refractory intracranial hypertension complicating diffuse TBI (2.3%). The median (intequartile range [IQR]) age was 35 (24, 58), and most injuries were caused by road traffic accidents (57.4%) or falls (25.1%). Overall, 34.3% of patients died while in the hospital and the remainder were discharged to rehabilitation (44.6%), other health care facilities (4.6%), or home (16.5%). There were no patient characteristics significantly associated with use of albumin or craniectomy. Intravenous albumin and craniectomy for treatment of intracranial hypertension were used infrequently in Australian neurotrauma centers, indicating alignment between best available evidence and practice.

Low-Value Clinical Practices in Adult Traumatic Brain Injury: An Umbrella Review.

Despite numerous interventions and treatment options, the outcomes of traumatic brain injury (TBI) have improved little over the last 3 decades, which raises concern about the value of care in this patient population. We aimed to synthesize the evidence on 14 potentially low-value clinical practices in TBI care. Using umbrella review methodology, we identified systematic reviews evaluating the effectiveness of 14 potentially low-value practices in adults with acute TBI. We present data on methodological quality (Assessing the Methodological Quality of Systematic Reviews), reported effect sizes, and credibility of evidence (I to IV). The only clinical practice with evidence of benefit was therapeutic hypothermia (credibility of evidence II to IV). However, the most recent meta-analysis on hypothermia based on high-quality trials suggested harm (credibility of evidence IV). Meta-analyses on platelet transfusion for patients on antiplatelet therapy were all consistent with harm but were statistically non-significant. For the following practices, effect estimates were consistently close to the null: computed tomography (CT) in adults with mild TBI who are low-risk on a validated clinical decision rule; repeat CT in adults with mild TBI on anticoagulant therapy with no clinical deterioration; antibiotic prophylaxis for external ventricular drain placement; and decompressive craniectomy for refractory intracranial hypertension. We identified five clinical practices with evidence of lack of benefit or harm. However, evidence could not be considered to be strong for any clinical practice as effect measures were imprecise and heterogeneous, systematic reviews were often of low quality, and most included studies had a high risk of bias.

Surgical complications of decompressive craniectomy in patients with head injury.

Decompressive craniectomy is an important method for managing refractory intracranial hypertension. Although decompressive craniectomy is arelatively simple procedure, various complications may arise. The aim of our paper was to determine the incidence of complications of decompressive craniectomy in patients with head injury and to analyse their risk factors. We retrospectively analysed agroup of 94 patients after decompressive craniectomy for head injury between 01 Jan 2014 and 31 Dec 2018. Postoperative complications were evaluated based on clinical examination and postoperative CT scan. The impact of potential risk factors on the occurrence of complications was assessed (age, worse initial clinical condition, any haemocoagulation disorder). Twenty patients died within the first month after surgery. Control CT scan showed one complication in 78 patients (83%), while 46 patients (49%) had more than one complication. We had to reoperate 22 patients (23.4%) due to acomplication. The following complications were found: postoperative acute subgaleal/subdural haematoma (30× - 32%), subgaleal/subdural cerebrospinal fluid effusion (29× - 31%), soft tissues oedema (29× - 31%), haemorrhagic progression of brain contusion (17× - 18%), malignant brain oedema (8× - 8.5%), hydrocephalus (8× - 8.5%), temporal muscle atrophy (7× - 7.5%), peroperative massive bleeding ( 6× - 6.4%), epilepsy (4× - 4.3%), syndrome of the trephined (2× - 2.1%), skin necrosis (2× - 2.1%). Patients with ahaemocoagulation disorder had asignificantly higher incidence of complications (p=0.01). Complications of decompressive craniectomy after head injury are frequent. The potential benefit of decompressive craniectomy can be adversely affected by the occurrence of many complications.

Intracranial Hypertension and Intra-abdominal Pressure. Is it Worth Measuring?

AbstractPatients with refractory intracranial hypertension who have already undergone all the measures recommended by the current guidelines can benefit from having their intra-abdominal pressure monitored since its increase generates hemodynamic repercussions and secondary elevation of intracranial pressure. In this context, a bibliographic research was performed on PubMed with the terms intra-abdominal pressure, abdominal compartment syndrome, intracranial pressure, intracranial hypertension. Altogether, 146 articles were observed, 87 of which were from the year 2000, and only 15 articles were considered relevant to the topic. These studies indicate that patients with refractory intracranial hypertension can benefit from the measurement of intraabdominal pressure, since there is evidence that an increase in this pressure leads to organic dysfunctions with an indirect impact on cerebral venous return and, consequently, an increase in intracranial pressure. In those who underwent decompression laparotomy, direct effects were observed in reducing intracranial hypertension and survival.

Elevated intracranial pressure after head trauma can be suppressed by antisecretory factor\u2014a pilot study

BackgroundControl of intracranial pressure (ICP) is a key element in neurointensive care for directing treatment decisions in patients with severe traumatic brain injury (TBI). The anti-inflammatory protein antisecretory factor (AF) has been demonstrated to reduce experimentally induced high ICP in animal models. This report describes the first steps to investigate the uptake, safety, and influence of AF for reduction of elevated ICP in patients with TBI in a clinical setting.MethodFour patients with severe TBI (Glasgow Coma Scale < 9) that required neurointensive care with ICP monitoring due to signs of refractory intracranial hypertension were investigated. One hundred milliliters of Salovum®, a commercially available egg yolk powder with high contents of AF peptides, was administrated either via nasogastric (patients 1 and 2) or rectal tube (patients 2, 3, and 4) every 8 h for 2 to 3 days as a supplement to the conventional neurointensive care. ICP was registered continuously. Plasma levels of AF were measured by enzyme-linked immunosorbent assay (ELISA) to confirm that Salovum® was absorbed appropriately into the bloodstream.ResultsIn the first two patients, we observed that when delivered by the nasogastric route, there was an accumulation of the Salovum® solution in the stomach with difficulties to control ICP due to impaired gastric emptying. Therefore, we tested to administer Salovum® rectally. In the third and fourth patients, who both showed radiological signs of extensive brain edema, ICP could be controlled during the course of rectal administration of Salovum®. The ICP reduction was statistically significant and was accompanied by an increase in blood levels of AF. No adverse events that could be attributed to AF treatment or the rectal approach for Salovum® administration were observed.ConclusionsThe outcomes suggest that AF can act as a suppressor of high ICP induced by traumatic brain edema. Use of AF may offer a new therapeutic option for targeting cerebral edema in clinical practice.

Cerebral edema with Refractory Intracranial Hypertension Secondary to Lamotrigine Overdose (5038)

Cerebral edema with Refractory Intracranial Hypertension Secondary to Lamotrigine Overdose (5038)

Noninvasive Monitoring and Neurointerventional Management of Idiopathic Intracranial Hypertension

AbstractIdiopathic intracranial hypertension (IIH) is characterized by isolated rise in intracranial pressure (ICP) leading to chronic, debilitating headaches, tinnitus, and vision loss. Conventional diagnostics and monitoring primarily require the use of invasive procedure like lumbar puncture to measure ICP, while traditional management strategies involve weight reduction and medical treatment with acetazolamide. In an effort to reduce the need for invasive procedures, noninvasive methods of ICP monitoring such as optic nerve sheath diameter measurements and two-depth transcranial Doppler ultrasonography have been developed. In cases of refractory and fulminant IIH, surgical management strategies such as optic nerve sheath fenestration (ONSF), ventriculoperitoneal (VP) and lumboperitoneal (LP) shunting, and transverse venous sinus stenting are used to relieve symptoms via ICP reduction. While ONSF and VP/LP shunting exhibit utility primarily for the treatment of vision loss and headache, respectively, venous sinus stenting may prove to be an effective option in the management of all symptoms of IIH. Most importantly, consideration of the patient’s individual symptoms and values should be taken into account when choosing the optimal surgical management strategy for patients with IIH.

Superonasal Transconjunctival Optic Nerve Sheath Decompression: A Simplified Technique for Safe and Efficient Decompression.

Severe, permanent vision loss is a feared sequela of untreated or refractory idiopathic intracranial hypertension (IIH). For patients with progressive vision loss despite maximally tolerated medical treatment, optic nerve sheath decompression (ONSD) remains a viable and effective option to protect vision. Our objective is to introduce a modified transconjunctival technique for ONSD and determine its safety, efficacy, and efficiency in patients with IIH. We performed analyses for a retrospective case series of consecutive patients with IIH by modified dandy criteria who underwent isolated superonasal transconjunctival optic nerve sheath decompression (stOND) at single eye institute in a large academic center from January 2013 to February 2017. Sixty-six patients were identified who met these criteria with at least 6 weeks of follow-up data. Primary outcome measures were visual field mean deviation, grading of papilledema by the modified Frisen scale, and best-corrected visual acuity. Secondary outcome measures were presence of postoperative diplopia and operative time. One hundred thirty-two eyes of 66 patients were identified; 58 were female (88%), and 8 were male (12%). The mean age was 30 years (range 13-55) with an average lumbar puncture opening pressure of 38 cm H2O. Participants mean body mass index was 36 (range 20-59) with Grade 3 papilledema on average by the modified Frisen scale. No patients experienced operative complications, postoperative diplopia, or worse visual acuity at 1 week after surgery. Average operative time was 50 minutes (range: 25-89). The median decrease in papilledema grading was 3 grades on the Frisen scale (95% confidence interval [CI], 2-3, P < 0.0001). Snellen visual acuity changes did not meet statistical significance. The average Humphrey Visual Field mean deviation change was +1.91 (95% CI, 0.58-3.24, P = 0.0052). Despite successful bilateral decompressions, 4 patients (6.1%) progressed in their visual loss. The superonasal transconjunctival approach to ONSD is a safe, efficient and effective surgical treatment for patients with deteriorating visual function due to IIH. Although additional study is required to further clarify the best timing and indications for ONSD among other treatment options for refractory IIH, providers should be aware of the reduced complication rates and efficacy of the stOND technique.

Patient Outcomes at Twelve Months after Early Decompressive Craniectomy for Diffuse Traumatic Brain Injury in the Randomized DECRA Clinical Trial.

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension.In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients.We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model.At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p = 0.04) outcomes.Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p = 0.01) were increased.Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors.

Intracranial pressure-based barbiturate coma treatment in children with refractory intracranial hypertension due to traumatic brain injury.

Refractory intracranial pressure (ICP) hypertension following traumatic brain injury (TBI) is a severe condition that requires potentially harmful treatment strategies such as barbiturate coma. However, the use of barbiturates may be restricted due to concerns about inducing multiorgan system complications related to the therapy. The purpose of this study was to evaluate the outcome and occurrence of treatment-related complications to barbiturate coma treatment in children with refractory intracranial hypertension (RICH) due to TBI in a modern multimodality neurointensive care unit (NICU). The authors conducted a retrospective cohort study of 21 children ≤ 16 years old who were treated in their NICU between 2005 and 2015 with barbiturate coma for RICH following TBI. Demographic and clinical data were acquired from patient records and physiological data from digital monitoring system files. The median age of these 21 children was 14 years (range 2-16 years) and at admission the median Glasgow Coma Scale score was 7 (range 4-8). Barbiturate coma treatment was added due to RICH at a median of 46 hours from trauma and had a median duration of 107 hours. The onset of barbiturate coma resulted in lower ICP values, lower pulse amplitudes on the ICP curve, and decreased amount of A-waves. No major disturbances in blood gases, liver and kidney function, or secondary insults were observed during this period. Outcome 1 year later revealed a median Glasgow Outcome Scale score of 5 (good recovery), however on the King's Outcome Scale for Childhood Head Injury, the median was 4a (moderate disability). The results of this study indicate that barbiturate coma, when used in a modern NICU, is an effective means of lowering ICP without causing concomitant severe side effects in children with RICH and was compatible with good long-term outcome.

Physiological Signatures of Brain Death Uncovered by Intracranial Multimodal Neuromonitoring.

The physiological and neurochemical changes that accompany brain death are not well described. A retrospective observational study of patients with acute brain injury who underwent intracranial multimodality neuromonitoring between October 2015 and June 2018. Patients were included for analysis either if brain death was diagnosed or refractory intracranial hypertension with persistent equalization of intracranial pressure (ICP) and mean arterial pressure (MAP) developed. Of 114 patients who underwent invasive neuromonitoring, 11 cases with MAP/ICP equalization were identified. Of those, 9 were declared brain dead based on accepted national and institutional criteria. An additional 2 cases with MAP/ICP equalization who died after withdrawal of life-sustaining therapies were identified. Of the 11 identified patients, 10 had continuous monitoring data available for analysis. Cerebral microdialysis data were available for 4 patients.In the 10 cases with available continuous data, ICP/MAP equalization was associated with marked reduction of cerebral blood flow and brain tissue oxygen tension to near zero levels as well as a significant decrease in brain temperature compared with body temperature. In the 4 patients with microdialysis monitoring, ICP/MAP equalization resulted in a near complete depletion of cerebral glucose and pyruvate, as well as a marked rise in cerebral glycerol. Finally, ICP/MAP equalization was accompanied by complete loss of cerebrovascular pressure reactivity, decrease in intracranial pulse pressure, and a paradoxical improvement of ICP waveform morphology. A characteristic set of changes in cerebrovascular physiology and neurochemistry occurs during brain death. These changes can be identified by intracranial neuromonitoring.

Examining the Effect of Hypertonic Saline Administered for Reduction of Intracranial Hypertension on Coagulation

Hypertonic saline (23.4%, HTS) bolus administration is common practice for refractory intracranial hypertension, but its effects on coagulation are unknown. We hypothesize that 23.4% HTS in whole blood results in progressive impairment of coagulation invitro and invivo in a murine model of traumatic brain injury (TBI). For the invitro study, whole blood was collected from 10 healthy volunteers, and citrated native thrombelastography was performed with normal saline (0.9%, NS) and 23.4% HTS in serial dilutions (2.5%, 5%, and 10%). For the invivo experiment, we assessed the effects of 23.4% HTS bolus vs NS on serial thrombelastography and tail-bleeding times in a TBI murine model (n= 10 rats with TBI and 10 controls). For the invitro work, clinically relevant concentrations of HTS (2.5% dilution) shortened time to clot formation and increased clot strength (maximum amplitude) compared with control and NS. With higher HTS dosing (5% and 10% blood dilution), there was progressive prolongation of time to clot formation, decreased angle, and decreased maximum amplitude. In the invivo study, there was no significant difference in thrombelastography measurements or tail-bleeding times after bolus administration of 23.4% HTS compared with NS at 2.5% blood volume. At clinically relevant dilutions of HTS, there is a paradoxical shortening of time to clot formation and increase in clot strength invitro and no significant effects in a murine TBI model. However, with excess dilution, caution should be exercised when using serial HTS boluses in TBI patients at risk for trauma-induced coagulopathy.